This invention relates to the measurement of various forms of cholesterol in the bloodstream of mammals, the diagnosis of vascular disease or atherosclerosis from such measurements, and a method of raising HDL cholesterol levels.
Serum total cholesterol consists of both esterified and unesterified cholesterol fractions bound in varying amounts to several lipoprotein carriers. Approximately 71-75% of the total cholesterol is esterified, i.e. bonded to fatty esters. Unesterified (free) cholesterol, an insoluble, abrasive waxy alcohol, makes up about 25-29% of the total. Chylomicrons, very large particles containing essential lubricating lipids, are produced in the duodenum and jejunum and play a role in the absorption of the essential fatty acids and phospholipids needed to form lipoprotein particles. Chylomicrons transport triglycerides (TG) from the intestines to the liver.
Low-density lipoprotein (LDL), the major cholesterol carrier, is a spherical particle consisting of about 50% cholesterol, 20% protein and 25% phospholipids. Very low-density lipoprotein (VLDL), a liver-generated precursor of LDL, is a large particle composed of 15-25% cholesterol and, mainly, triglycerides. LDL and VLDL have been implicated in atherosclerosis. VLDL particles typically have a life span of 4-5 hours, while LDL particles last 2-3 days.
High-density lipoprotein (HDL), a small particle obtaining about 20% cholesterol, 50% protein, and 25% phospholipids, appears to play a major role in the exchange of free cholesterol between cells, the liver, and other lipoprotein moieties. Free cholesterol is needed in red blood cells, lipoprotein moieties, and most cell structures. High levels of HDL are believed to lower the incidence of cardiovascular disease.
Blood tests to determine total serum cholesterol are commonly used to assess the risk of heart disease. However, since not all types of cholesterol indicate high risk, total serum cholesterol is not a very reliable indicator below 300 mg/dl. Consequently, attempts have been made to separately measure the HDL fraction. Typically, the LDL and VLDL fractions are precipitated out of solution and the cholesterol entities remaining in the supernatant are measured. These entities are assumed to be HDL. However, due to the presence of free cholesterol, the supernatant liquid contains a mixture of HDL and free cholesterol particles. Since the cholesterol in the supernatant is not all HDL, the measured HDL value is erroneous. The amount of HDL reported may be from 15 to 30% higher than the true value. Because this error is not constant, conventional HDL measurement techniques do not provide an accurate guide for comparing the percentage of HDL in the total serum cholesterol of various subjects.
Those who are perceived to have a high risk of heart disease due to high cholesterol levels are often treated with a drug, e.g. lovastatin, to reduce their cholesterol levels. In addition, a low-cholesterol diet is generally suggested. The drug treatment is believed to work by suppressing cholesterol production in the liver. This treatment has several drawbacks: high cost; possible liver damage; and, other side effects. Because of the drawbacks, drug treatment is not recommended for most people in the moderate to high risk categories. Treatment is limited, in many cases, to recommending a low-cholesterol diet. While such a diet may be helpful, it is often not enough, particularly where a patient has difficulty staying on the diet.